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. 2022 Feb;192(1):19-32.
doi: 10.1007/s10549-021-06482-3. Epub 2022 Jan 12.

Low RUFY3 expression level is associated with lymph node metastasis in older women with invasive breast cancer

Fernando A Angarita #  1   2 , Masanori Oshi #  1   3 , Akimitsu Yamada  3 , Li Yan  4 , Ryusei Matsuyama  3 , Stephen B Edge  1   5 , Itaru Endo  3 , Kazuaki Takabe  6   7   8   9   10
Affiliations

Low RUFY3 expression level is associated with lymph node metastasis in older women with invasive breast cancer

Fernando A Angarita et al. Breast Cancer Res Treat. 2022 Feb.

Abstract

Purpose: Sentinel lymph node biopsy is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogeneous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women.

Methods: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts.

Results: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3-predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease-specific survival among older women.

Conclusion: Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.

Keywords: Axillary lymph node; Breast cancer; Geriatric oncology; RUFY3.

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Conflict of interest statement

Conflicts of interest/Competing interests: The authors declare that they have no conflict of interest.

Figures

FIG 1.
FIG 1.. Oncologic survival outcomes of patients in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Cancer Genome Atlas (TCGA) cohorts by axillary lymph node (LN) status involvement.
Kaplan-Meier disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) curves of the whole cohort (A) and older women (≥70 years old) in the METABRIC and TCGA cohorts. Comparison between LN-positive (blue line) and LN-negative (red line) patients was performed using log-rank test. The bottom one-third was used as cut-off value to divide two groups within cohorts.
FIG 2.
FIG 2.. RUFY3 is associated with lymph node metastasis in patients with breast cancer.
(a) Box plots depicting RUFY3 expression stratified lymph node involvement in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Cancer Genome Atlas (TCGA) cohorts. P-values were calculated by Mann-Whitney U test. (b) Receiver operator characteristic (ROC) curve showing the sensitivity and specificity of RUFY3 amongst older women and all age women. Abbreviations: N−, lymph node-negative; N+, lymph node-positive.
FIG 3.
FIG 3.. Gene Set Enrichment Analysis (GSEA) according to RUFY3 expression level in older women with breast cancer in the METABRIC and TCGA cohorts.
Enrichment plots with normalized enrichment score (NES) and false discovery rate (FDR) of hallmark gene sets which were significantly enriched in the low RUFY3 groups in both cohorts. Bottom one-third was used as cut-off value to divide two groups within cohorts.
FIG 4.
FIG 4.. Association of RUFY3 expression level with immune fraction in the tumor microenvironment, immune activity, intratumor heterogeneity, and mutation load.
Boxplots of (a) the infiltrating fraction of immune cells [CD8+ T cells, CD4+ T cells, T helper type1 (Th1) and type2 (Th2) cells, regulatory, M1 and M2 macrophages, and dendritic cells (DC)]; (b) cytolytic activity score (CYT); and (c) intratumor heterogeneity and mutation-related score [silent and non-silent mutation rate, fraction altered, single nucleotide variant (SNV) and indel neoantigens] stratified by RUFY3 expression level in older women with breast cancer.
FIG 5.
FIG 5.. Association of RUFY3 expression level on LN involvement and patient survival.
(a) Bar plots of lymph node metastasis rate by low and high RUFY3 level in whole age cohort and older women in the METABRIC and TCGA cohorts. (b) Kaplan-Meier curves of disease-specific survival in whole age and older women cohorts of the METABRIC cohort.
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References

    1. American Cancer Society. Breast cancer facts & figures 2019–2020. Atlanta, GA: American Cancer Society, Inc; 2019.
    1. Lodi M, Scheer L, Reix N, et al. (2017) Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review. Breast Cancer Res Treat 166:657–668. - PubMed
    1. Hughes KS, Schnaper LA, Bellon JR, et al. (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31:2382–2387. - PMC - PubMed
    1. Kiderlen M, de Glas NA, Bastiaannet E, et al. (2014) Impact of comorbidity on outcome of older breast cancer patients: a FOCUS cohort study. Breast Cancer Res Treat 145:185–192. - PubMed
    1. Muss HB, Berry DA, Cirrincione C, et al. (2007) Toxicity of older and younger patients treated with adjuvant chemotherapy for node positive breast cancer: the cancer and Leukemia group B experience. J Clin Oncol 25:3699–3704. - PubMed